title: miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.
abstract: Tumor progression is accompanied by an altered myelopoiesis causing the accumulation of immunosuppressive cells. Here, we showed that miR-142-3p downregulation promoted macrophage differentiation and determined the acquisition of their immunosuppressive function in tumor. Tumor-released cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP∗ isoform of C/EBPβ transcription factor, promoting macrophage generation. miR-142-3p downregulated gp130 by canonical binding to its messenger RNA (mRNA) 3' UTR and repressed C/EBPβ LAP∗ by noncanonical binding to its 5' mRNA coding sequence. Enforced miR expression impaired macrophage differentiation both in vitro and in vivo. Mice constitutively expressing miR-142-3p in the bone marrow showed a marked increase in survival following immunotherapy with tumor-specific T lymphocytes. By modulating a specific miR in bone marrow precursors, we thus demonstrated the feasibility of altering tumor-induced macrophage differentiation as a potent tool to improve the efficacy of cancer immunotherapy.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Oncology and Immunology Section, University of Padua, 35128 Padua, Italy.
authors.forename: Nada
authors.initials: N
authors.lastname: Sonda
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonato
authors.forename: Elisa
authors.initials: E
authors.lastname: Peranzoni
authors.forename: Bianca
authors.initials: B
authors.lastname: Calì
authors.forename: Stefania
authors.initials: S
authors.lastname: Bortoluzzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Bisognin
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gentner
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Sara Dutton
authors.initials: SD
authors.lastname: Sackett
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
authors.forename: Barbara
authors.initials: B
authors.lastname: Molon
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D038042:Myelopoiesis / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D019076:Transgenes / Q000235:genetics; D019139:Tumor Escape
chemical_list: D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D012333:RNA, Messenger; D050822:Cytokine Receptor gp130; C490380:Ebp protein, mouse; D013251:Steroid Isomerases